Dual-Targeting Temozolomide Loaded in Folate-Conjugated Magnetic Triblock Copolymer Nanoparticles to Improve the Therapeutic Efficiency of Rat Brain Gliomas

ACS Biomater Sci Eng. 2019 Nov 11;5(11):6000-6011. doi: 10.1021/acsbiomaterials.9b00856. Epub 2019 Oct 17.

Abstract

In order to conduct an effective chemotherapy session as a treatment modality for glioblastoma tumors, a nanocarrier platform is required for the drug to cross the blood brain barrier (BBB) successfully and properly target glioma cells. Dual-targeting Temozolomide (TMZ) loaded triblock polymer coated magnetic nanoparticles (MNPs) were synthesized with a SPION core and by conjugating the surface with folic acid (FA), which were shown to effectively pass the BBB and target tumor cells. Two principal methods, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were employed for characterization of the synthesized nanoparticles. TMZ-loaded MNP-FA nanoparticles presented with a size of 58.61 nm, a zeta potential of -29.85 ± 0.47 mV, and a drug loading content of 6.85 ± 0.46%. Data gathered from inductively coupled plasma optical emission spectrometry (ICP-OES) and Prussian blue staining indicated effective dual-targeting, which subsequently led to an appreciably enhanced penetration through the BBB and accumulation of MNPs-FA in rat glioma cells. The anticancer effect of the dual-targeting MNPs-FA was also indicated by the increased survival time (>100%, p < 0.001) and decreased tumor volume (p < 0.001). In conclusion, the dual-targeting TMZ-loaded MNPs-FA are able to improve therapeutic efficiency toward brain gliomas in rats.

Keywords: blood brain barrier; dual-targeting; folate; glioblastoma; magnetic targeting.